title: Duodenal nutrient exclusion improves metabolic syndrome and stimulates villus hyperplasia.
abstract: OBJECTIVE
  Surgical interventions that prevent nutrient exposure to the duodenum are among the most successful treatments for obesity and diabetes. However, these interventions are highly invasive, irreversible and often carry significant risk. The duodenal-endoluminal sleeve (DES) is a flexible tube that acts as a barrier to nutrient-tissue interaction along the duodenum. We implanted this device in Zucker Diabetic Fatty (ZDF) rats to gain greater understanding of duodenal nutrient exclusion on glucose homeostasis.
  
  
  METHODS
  ZDF rats were randomised to four groups: Naive, sham ad libitum, sham pair-fed, and DES implanted. Food intake, body weight (BW) and body composition were measured for 28 days postoperatively. Glucose, lipid and bile acid metabolism were evaluated, as well as histological assessment of the upper intestine.
  
  
  RESULTS
  DES implantation induced a sustained decrease in BW throughout the study that was matched by pair-fed sham animals. Decreased BW resulted from loss of fat, but not lean mass. DES rats were also found to be more glucose tolerant than either ad libitum-fed or pair-fed sham controls, suggesting fat mass independent metabolic benefits. DES also reduced circulating triglyceride and glycerol levels while increasing circulating bile acids. Interestingly, DES stimulated a considerable increase in villus length throughout the upper intestine, which may contribute to metabolic improvements.
  
  
  CONCLUSIONS
  Our preclinical results validate DES as a promising therapeutic approach to diabetes and obesity, which offers reversibility, low risk, low invasiveness and triple benefits including fat mass loss, glucose and lipid metabolism improvement which mechanistically may involve increased villus growth in the upper gut.
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, Metabolic Diseases Institute, Obesity Research Center, University of Cincinnati, Cincinnati, Ohio, USA.
authors.forename: Kirk M
authors.initials: KM
authors.lastname: Habegger
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, Metabolic Diseases Institute, Obesity Research Center, University of Cincinnati, Cincinnati, Ohio, USA.
authors.forename: Omar
authors.initials: O
authors.lastname: Al-Massadi
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, Metabolic Diseases Institute, Obesity Research Center, University of Cincinnati, Cincinnati, Ohio, USA.
authors.forename: Kristy M
authors.initials: KM
authors.lastname: Heppner
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
authors.forename: Andriy
authors.initials: A
authors.lastname: Myronovych
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, Metabolic Diseases Institute, Obesity Research Center, University of Cincinnati, Cincinnati, Ohio, USA.
authors.forename: Jenna
authors.initials: J
authors.lastname: Holland
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, Metabolic Diseases Institute, Obesity Research Center, University of Cincinnati, Cincinnati, Ohio, USA.
authors.forename: Jose
authors.initials: J
authors.lastname: Berger
authors.affiliation: Institute for Diabetes and Obesity, Helmholtz Zentrum München and Technische Universität München, Munich, Germany.
authors.forename: Chun-Xia
authors.initials: CX
authors.lastname: Yi
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, Metabolic Diseases Institute, Obesity Research Center, University of Cincinnati, Cincinnati, Ohio, USA.
authors.forename: Yuanging
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, Metabolic Diseases Institute, Obesity Research Center, University of Cincinnati, Cincinnati, Ohio, USA.
authors.forename: Maarit
authors.initials: M
authors.lastname: Lehti
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, Metabolic Diseases Institute, Obesity Research Center, University of Cincinnati, Cincinnati, Ohio, USA.
authors.forename: Nickki
authors.initials: N
authors.lastname: Ottaway
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, Metabolic Diseases Institute, Obesity Research Center, University of Cincinnati, Cincinnati, Ohio, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Amburgy
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, Metabolic Diseases Institute, Obesity Research Center, University of Cincinnati, Cincinnati, Ohio, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Raver
authors.affiliation: Institute for Diabetes and Obesity, Helmholtz Zentrum München and Technische Universität München, Munich, Germany.
authors.forename: Timo D
authors.initials: TD
authors.lastname: Müller
authors.affiliation: Institute for Diabetes and Obesity, Helmholtz Zentrum München and Technische Universität München, Munich, Germany.
authors.forename: Paul T
authors.initials: PT
authors.lastname: Pfluger
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
authors.forename: Rohit
authors.initials: R
authors.lastname: Kohli
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, Metabolic Diseases Institute, Obesity Research Center, University of Cincinnati, Cincinnati, Ohio, USA.
authors.forename: Diego
authors.initials: D
authors.lastname: Perez-Tilve
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, Metabolic Diseases Institute, Obesity Research Center, University of Cincinnati, Cincinnati, Ohio, USA.
authors.forename: Randy J
authors.initials: RJ
authors.lastname: Seeley
authors.affiliation: Institute for Diabetes and Obesity, Helmholtz Zentrum München and Technische Universität München, Munich, Germany.
authors.forename: Matthias H
authors.initials: MH
authors.lastname: Tschöp
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism*; D001823:Body Composition; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000628:therapy; D004386:Duodenum / Q000473:pathology / Q000502:physiology*; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D005951:Glucose Tolerance Test; D005990:Glycerol / Q000097:blood; D006706:Homeostasis; D007082:Ileum / Q000473:pathology; D007408:Intestinal Absorption; D007583:Jejunum / Q000473:pathology; D008297:Male; D024821:Metabolic Syndrome / Q000628:therapy*; D009765:Obesity / Q000628:therapy; D019736:Prostheses and Implants; D011897:Random Allocation; D051381:Rats; D011924:Rats, Zucker; D014280:Triglycerides / Q000097:blood
chemical_list: D001647:Bile Acids and Salts; D001786:Blood Glucose; D014280:Triglycerides; D052216:Glucagon-Like Peptide 1; D005990:Glycerol
keywords: BASIC SCIENCES; ENDOCRINE HORMONES; GASTROINTESTINAL ENDOCRINOLOGY; OBESITY; OBESITY SURGERY